title: Dynamic stabilization of actin filaments.
abstract: We report here that actin filaments in vitro exist in two populations with significantly different shrinkage rates. Newly polymerized filaments shrink rapidly, primarily from barbed ends, at 1.8/s, but as they age they switch to a stable state that shrinks slowly, primarily from pointed ends, at approximately 0.1/s. This dynamic filament stabilization runs opposite to the classical prediction that actin filaments become more unstable with age as they hydrolyze their bound ATP and release phosphate. Upon cofilin treatment, aged filaments revert to a dynamic state that shows accelerated shrinkage from both ends at a combined rate of 5.9/s. In light of recent electron microscopy studies [Orlova A, et al. (2004) Actin-destabilizing factors disrupt filaments by means of a time reversal of polymerization. Proc Natl Acad Sci USA 101:17664-17668], we propose that dynamic stabilization arises from rearrangement of the filament structure from a relatively disordered state immediately after polymerization to the canonical Holmes helix, a change that is reversed by cofilin binding. Our results suggest that plasticity in the internal structure of the actin filament may play a fundamental role in regulating actin dynamics and may help cells build actin assemblies with vastly different turnover rates.
authors.affiliation: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Hao Yuan
authors.initials: HY
authors.lastname: Kueh
authors.forename: William M
authors.initials: WM
authors.lastname: Brieher
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchison
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006868:Hydrolysis; D007700:Kinetics; D018482:Muscle, Skeletal / Q000166:cytology; D011487:Protein Conformation; D011817:Rabbits
chemical_list: D051339:Actin Depolymerizing Factors; D000255:Adenosine Triphosphate